Purpose
GnRH analogs are useful for the treatment of prostate cancer, but require parenteral administration. The peptide GnRH antagonist acyline potently suppresses luteinizing hormone (LH) and testosterone in man; however, its clinical utility is limited by the requirement for frequent injections. The use of a proprietary enhancer system called GIPET®, which is based on medium-chain fatty acids, facilitates the oral bioavailability of peptides. We hypothesized that GIPET® enhancement would allow for the safe oral dosing of acyline for the treatment of prostate cancer.
Methods
We enrolled eight healthy young men in a pharmacokinetic and pharmacodynamic study of 10, 20 and 40 mg doses of GIPET®-enhanced oral acyline. Blood for measurement of serum LH, FSH, testosterone and acyline was obtained prior to each dose of GIPET®-enhanced oral acyline and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 h after dosing.
Results
Serum LH, FSH and serum testosterone were significantly suppressed by all doses of GIPET®-enhanced oral acyline after 6 h, with suppression reaching a nadir 12 h after dosing. In addition, the 20 and 40 mg doses demonstrated sustained suppression of testosterone for 12–24 h. All hormone concentrations returned to normal 48 h after administration. There were no treatment-related serious adverse events, and laboratory assessments, including liver function tests and creatinine, were unaffected by treatment.
Conclusions
Oral administration of GIPET®-enhanced acyline significantly suppresses testosterone and gonadotropins in normal men without untoward side effects and might have utility in the management of prostate cancer.